The structure and biogenesis of cell memebranes in normal and cancer cells will be studied using the techniques of somatic cell genetics. Differences will be studied in order to evaluate the genetic and epigenetic basis for malignancy and to evaluate possibilities of exploiting these differences in the design to cancer chemotherapy. We will use mammalian cell mutants resistant to ricin to study the properties of the ricin receptors on the cell surface. Genetic complementation by intraspecific cell hybridization will be performed to classify the types of genetic alterations involved. Interspecific cell hybrids between toxin or lectin resistant mutant mouse cells and normal human cells will be constructed to assign the gene responsible for particular phenotypes to specific human chromosomes. We have derived fluorescent latex microspheres conjugated to diphtheria toxin. Use will be made of these affinity labeled microspheres for the purpose of developing a positive selective method for isolating human-rodent hybrids that have the toxin receptors. If this method is successful, it will be extended to include other toxins and lectins as positive selective agents.